Female pattern hair loss (alopecia) affects approximately 20 million women. Hair loss begins at puberty and progresses throughout life. Early detection of the condition is difficult, which is unfortunate, since early diagnosis and treatment are important in achieving optimal therapy. While the pattern of hair loss varies considerably, a decreased hair count over the entire top of the scalp commonly occurs. A good indicator of female pattern hair loss is a widening part line or a thinning ponytail. Typically, daily hair loss counts do not exceed 100-125 hairs; however hair follicles that enter the telogen phase do not reenter the anagen growth phase, resulting in a slow net loss of active follicles. The treatment options for this condition are limited and include hair transplants, hormonal supplementation and minoxidil, a drug that affects calcium homeostasis. See, Li, et al., J Invest Dermatol, 117(6):1594-1600 (2001). Topical 2% and minoxidil, the only approved drug therapies for this condition.
The limited treatment options available for female alopecia has led to the search for other agents that can provide benefit for this condition. A potential candidate for hair growth promotion is niacin (nicotinic acid). Studies have identified several possible mechanisms suggesting that nicotinic acid may benefit these conditions. The major bioactive form of niacin, nicotinamide adenine dinucleotide (NAD) plays a central role in cellular energy metabolism and, the hair follicle has high energy requirements (Jacobson, et al., J Photochem Photobiol B 63(1-3):141-7 (2001)). NAD is also the substrate for enzymes involved in the maintenance of genomic integrity Jacobson, et al., Trends Biochem Sci, 24(11):415-417 (1999)) and calcium homeostasis (Lee, Curr. Mol. Med., 4(3):227-237 (2004)). Additionally, skin has been shown to contain niacin receptors that stimulate leptin release (Kim, et al., J. Invest. Dermatol., 119:347 (2002)) and downstream regulators in the leptin pathway are involved in skin homeostasis (Komuves, et al., J Invest Dermatol, 115(3):361-367 (2000)) and hair follicle cycling (Sano, et al., EMBO J., 18(17):4657-4668 (1999)). While either niacin or its other vitamin form, niacinamide, have the potential to be converted to NAD, the nicotinic acid receptor responds only to niacin (Tunaru, et al., Nat. Med., 9(3):352-355 (2003)).
While niacin has the potential to provide benefit to skin and scalp, delivery of niacin per se is not feasible in appreciable amounts, as it causes intense vasodilation at the site of application and its physical properties do not allow it to achieve a prolonged residence time in the skin. This has led to the development of myristyl nicotinate, a niacin derivative that effects delivery to skin cells without vasodilation and creates a residence time allowing conversion to NAD (Jacobson, et al., J. Invest. Dermatol., 114:849 (2000), and U.S. Pat. No. 6,337,065, both of which are incorporated by reference) and stimulation of the nicotinic acid receptor. (Tunaru, et al., supra). Myristyl nicotinate has been shown to promote epidermal differentiation leading to strong enhancement of skin barrier integrity (Jacobson, et al., in Alberts, et al., ed. Fundamentals of Cancer Prevention (Springer, 2005, pgs. 139-160). Another niacin derivative, octyl nicotinate, stimulates blood flow and oxygen delivery to tissue. See, e.g., U.S. Pat. No. 6,924,299, incorporated by reference in its entirety. The '299 patent, however, is silent as to the use of the described compounds in the context of hair growth or, treatment of disorders of hair growth, or any related conditions.
A feature of the invention thus relates to methods for treating hair growth disorders, such as female pattern, baldness, or alopecia, via the administration of one or more nicotinic acid alkyl esters. In some cases, administration of one of these compounds will be sufficient, whereas in other scenarios, mixtures of two or more in a composition or formulation, will be desired.
When two or more of these nicotinic acid alkyl esters are used in composition form, such compositions are also a feature of this invention.
Further features of the invention and its operation will be clear from the discussion which follows.